3tti

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{{STRUCTURE_3tti| PDB=3tti | SCENE= }}
 
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===Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor===
 
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{{ABSTRACT_PUBMED_22244937}}
 
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==Disease==
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==Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor==
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[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[http://omim.org/entry/606369 606369]]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
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<StructureSection load='3tti' size='340' side='right'caption='[[3tti]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3tti]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TTI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KBI:TRANS-4-({9-[(3S)-TETRAHYDROFURAN-3-YL]-8-[(2,4,6-TRIFLUOROPHENYL)AMINO]-9H-PURIN-2-YL}AMINO)CYCLOHEXANOL'>KBI</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tti OCA], [https://pdbe.org/3tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tti RCSB], [https://www.ebi.ac.uk/pdbsum/3tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tti ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:[https://omim.org/entry/606369 606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
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== Function ==
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[https://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>
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==Function==
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==See Also==
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[[http://www.uniprot.org/uniprot/MK10_HUMAN MK10_HUMAN]] Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons.<ref>PMID:11718727</ref>
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*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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[[3tti]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TTI OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:022244937</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mitogen-activated protein kinase]]
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[[Category: Large Structures]]
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[[Category: Albers, R.]]
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[[Category: Albers R]]
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[[Category: Ayala, L.]]
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[[Category: Ayala L]]
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[[Category: Bahmanyar, S.]]
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[[Category: Bahmanyar S]]
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[[Category: Bai, A.]]
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[[Category: Bai A]]
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[[Category: Benish, B.]]
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[[Category: Benish B]]
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[[Category: Bennett, B.]]
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[[Category: Bennett B]]
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[[Category: Blease, K.]]
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[[Category: Blease K]]
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[[Category: Bodine, T.]]
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[[Category: Bodine T]]
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[[Category: Cathers, B E.]]
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[[Category: Cathers BE]]
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[[Category: Celeridad, M.]]
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[[Category: Celeridad M]]
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[[Category: Chamberlain, P.]]
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[[Category: Chamberlain P]]
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[[Category: Clareen, S.]]
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[[Category: Clareen S]]
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[[Category: Delgado, M.]]
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[[Category: D'Sidocky N]]
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[[Category: Delker, S L.]]
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[[Category: Delgado M]]
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[[Category: Fan, R.]]
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[[Category: Delker SL]]
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[[Category: Giegel, D.]]
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[[Category: Fan R]]
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[[Category: Hegde, S.]]
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[[Category: Giegel D]]
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[[Category: Hilgraf, R.]]
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[[Category: Hegde S]]
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[[Category: Katz, J.]]
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[[Category: Hilgraf R]]
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[[Category: Khatsenko, O.]]
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[[Category: Katz J]]
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[[Category: Lachowitzer, J.]]
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[[Category: Khatsenko O]]
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[[Category: McCarrick, M.]]
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[[Category: Lachowitzer J]]
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[[Category: Moghaddam, M.]]
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[[Category: McCarrick M]]
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[[Category: Muir, J.]]
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[[Category: Moghaddam M]]
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[[Category: Nadolny, L.]]
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[[Category: Muir J]]
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[[Category: Plantevin-Krenitsky, V.]]
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[[Category: Nadolny L]]
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[[Category: Raymon, H.]]
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[[Category: Plantevin-Krenitsky V]]
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[[Category: Sapienza, J.]]
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[[Category: Raymon H]]
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[[Category: Satoh, Y.]]
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[[Category: Sapienza J]]
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[[Category: Shirley, M A.]]
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[[Category: Satoh Y]]
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[[Category: Sidocky, N D.]]
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[[Category: Shirley MA]]
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[[Category: Tang, Y.]]
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[[Category: Tang Y]]
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[[Category: Wright, J.]]
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[[Category: Wright J]]
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[[Category: Xu, L.]]
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[[Category: Xu L]]
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[[Category: Jnk3]]
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[[Category: Kinase]]
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[[Category: Mitogen-activated protein kinase 10]]
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[[Category: Protein kinase inhibitor]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor

PDB ID 3tti

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